Abstract

Introduction: The rabbit small clot embolic model for large vessel occlusion (LVO) is well established, yet remains with limitations. Blind introduction of autologous thrombus often fails to occlude the target vessel, and when successful, the precise timing of occlusion and revascularization are difficult to control. Studies of cellular biology and neuroimaging of acute reversible cerebral ischemia (i.e., penumbral tissue) would benefit from a rabbit model in which LVO can be reliably induced and easily confirmed, where the time of occlusion and revascularization can be precisely controlled. Hypothesis: We hypothesized that microcatheterization of the posterior cerebral artery (PCA) in New Zealand white rabbits (NZWRs) would result in LVO, with time of revascularization controlled by microcatheter removal. We hypothesized that transient LVO would produce ischemia in subcortical structures supplied by the PCA (e.g., hippocampus), sparing the cortex, with longer duration LVO leading to irreversible cortical ischemia. Methods: Transfemoral 1.5F microcatheterization of the PCA was performed in anesthetized NZWRs using fluoroscopic guidance. LVO was maintained for 30 minutes (n=2), 60 minutes (n=2), 180 minutes (n=2) and 210 minutes (n=1), followed by microcatheter removal and reperfusion. Neuroimaging was obtained 3 hours later with MRI (3T DWI, FLAIR, gradient and perfusion sequences) and CT (64 slice noncontrast and perfusion imaging). Post-mortem histologic analysis of infarct was assessed using triphenyltetrazolium choloride (TTC) stain. Matched DWI and TTC sections were analyzed using ImageJ software. Results: Percent infarct of matched DWI and TTC sections was strongly correlated (r2 = 0.86). Transient LVO of 30-60 minutes resulted in infarction of the ipsilateral hippocampus and thalamus, sparing the cortex, while more prolonged LVO (180-210 minutes) led to cortical infarction as well. Conclusions: Image-guided microcatheter induction of LVO in NZW rabbits can reliably produce time-dependent infarction of cortical and subcortical structures, and thus may be a useful model for the study of penumbral cortical tissue.

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